May 15, 2020 Avoiding Hospital Visits and an Update on COVID-19 and Diabetes

0:15 Grace Leeder: Okay. So, welcome everyone to another webinar in our COVID-19 and Diabetes webinar series, brought to you by Diabetes Canada. Today Dr. Alice Cheng, very excited to have her back to talk about avoiding hospital visits. This is part two of a two part series. Part One was last Friday with Catherine Yu and Susie Jin. And also, Alice is going to give us an update on COVID-19 and Diabetes, so very excited for today's presentation. Just having some trouble with my slides. Sorry. So today's webinar was supported by Lilly, so we really appreciate their, their support in bringing you today's presentation. And so we're going to start off with doing some polling questions. So first we just like to know what is your profession, so can see those listed there should have popped up in a window and we'll give it about 30 seconds and then we'll see who we have joining us today.

1:38 Thanks for participating in the poll, looks like we have about a third registered nurses and a third registered dietitians. We have some nurse practitioners. Some pharmacists joining us and endocrinologists a couple of researchers, some students and then 10% other and our second question today is, we just want to know where you are viewing the presentation from.

2:22 Okay great, thanks. So, um, as has been the case with our webinars about 50% of our audience is from Ontario, but we do have representation from pretty much every province across the country. So that's really great to see. So thank you for that. If you have any questions during today's presentation, feel free to type them in the Q&A box and Alice will answer them at the end of the presentation, say, but without further ado, I'll pass it over to Dr. Cheng.

2:50 Alice Cheng: Great. So thank you very much grace for the kind introduction and for getting things started. I'm going to share my slides here. So it's a pleasure to be back. It's a pleasure to be back speaking to all of you and it’s what, now May 15. And I think we started this webinar series back around March 20 something, if I'm not mistaken. And since then there have been a number of fantastic sessions that have been run from by our colleagues across the country, and I certainly want to thank everybody for that. And today I'm going to be doing part two of the avoiding hospital visits and I'll also do a little bit of an update on COVID-19 and diabetes, given how quickly the data are changing and being updated on a very regular basis.

3:40 So these are my disclosures. I've worked in some capacity rather pretty much with every diabetes company, mostly in the form of education or in the form of consulting.

3:50 And as I said, this is part two, right. So this was part one. Part one was delivered last Friday by Dr Catherine Yu and Susie Jin. And if anybody wasn't sure whether or not they were friends already. I found this picture on the internet, interestingly, if you search their names and as a picture of them, it looks like at the DC conference, I'm not sure when. So they're definitely good friends as well and did a fantastic job of talking about some components of how to keep people out of hospital. And keeping people out of hospital is one of our goals is outpatient practitioners, all the time, but particularly during this crazy time. And they very nicely went over ways to avoid DKA or hyperosmolar nonketotic. Ways to avoid marked hyperglycemic amongst patients and they interspaced it quite nicely with some cases to illustrate some of those details. And of course, lots of details around sick day management, which is how you're going to be able to help avoid those two things above. And today what I'm going to focus more on is the fourth component which is avoiding hypoglycemia, which of course is the other diabetes specific related reason that people may need to go to hospital. And there, it's about choosing therapies wisely and as well as offering therapies wisely in order to help those patients to avoid having to go to emerge.

5:09 Now we're focusing on hypoglycemia. I assume everybody on the call is very familiar already with the definition of hypoglycemia. This is the definition that's been put into our Diabetes Canada guidelines, but it's also known as Whipple’s Triad. So if you're ever doing medical jeopardy, this would be one of the my favorite Jeopardy questions actually. So Professor Whipple described hypoglycemia as development of symptoms consistent with hypoglycemia, objective evidence of low blood sugars as well as response to a carbohydrate load. Very simple, very elegant definition and most elegant things are actually simple and this I think falls into that category. And as you well know, the severity of hypoglycemia is categorized based on mild, moderate, or severe. And severe hypoglycemia is classically known as hypoglycemia requiring somebody else to help you. So if you're having hypoglycemia able to help yourself, that's not yet considered severe. But if you're having hypoglycemia, and either you fail to recognize it and someone has to help you or you recognize it, but you cannot get up out of your chair to go get something to help yourself, that qualifies as severe hypoglycemia. And unconsciousness may be a component, but does not have to be a component and the plasma glucose is typically less than 2.8 millimoles per liter. But that's sort of the definition and classification of hypoglycemia, that that Canada has adopted and many parts of the world had for a long time. However, very recently there have been some discussions about modifying that definition of hypoglycemia, particularly in the context of clinical trials. And therefore, the International Hypoglycemia Study Group has suggested the following. That a plasma glucose concentration of 3.9 or less is a glucose alert value. And that it's really less than three, that would be considered serious or clinically important hypoglycemia. And that there is no specific threshold for severe hypoglycemia, but severe hypoglycemia continues to be defined as requiring assistance from somebody else. So this has been suggested as well. And it's something that you will hear people talk about the different levels of hypoglycemia and that's based on this international hypoglycemia study group and it is worthwhile mentioning that this study group, though, was not just made up of clinicians and researchers, but of course included the most important population, which were people living with diabetes.

7:47 So, why talk about hypoglycemia in the context of a series discussing avoiding going to hospital well these are data very recent data, I think, published in about January of this year, looking at 201,705 adults with diabetes in a particular us administrative claims database. And what they found was that hypo related emergency room visits and hospitalizations about 9.06 per thousand person years. And what were the factors that increase the risk of having a hypo related emergency room or hospital visit. Well, one of them was age. So as you can see here the events per thousand person years on the Y axis goes up as you go up in age and the highest being those 75 plus. And annual household income was also an association and that likely has to relate to the the social determinants of health and how much socio economic status does in fact impact health care and also health outcomes. And then other things that came up were total comorbidities. And we saw those types of data from other studies in the past showing that people who had lots of things wrong with them were people who had more severe hypoglycemic episodes, but the reverse was true. People who had the severe hypoglycemia episodes were also the people with more things wrong with them. And what's not clear, is what's so what's what's cause and effect. But the point is, those with more comorbidities also had more hospital and emergency room visits. And then this is the curve for A1C which may be a little counterintuitive, although I'd say the data and the last 10 years or so have certainly supported this. The data that we knew from DCCT and type one diabetes suggested, not a curve that looks like this, it's suggested that the lower your A1C, the more hypo you got. However, I think data, then that started to come out from the type two diabetes glycemic control trials suggested that things may actually be a little bit different. And in fact, the people with the lowest A1Cs, so here in the less than 5.6, yes, had a little bit more but there seemed to be a sweet spot within what we would consider the usual targets for A1C and as a A1C went up there actually was more severe hypoglycemia. So that may actually be more of a marker of the overall health care that the person is receiving and their ability to manage at home. And then what about comorbidities. So this is a variety of co-morbidities listed and then you see the events per thousand person years. And ESRD clearly stands out as a winner if you will of increasing the potential for someone having a hospital related severe hypoglycemic event, but other things that stand out are proliferative retinopathy, interestingly. So no we don't think that having eye disease directly causes hypo, of course. But that association is obvious, and that people with proliferative retinopathy are more likely to have other opothies from diabetes and then you'll see that dementia is also on their falls, etc, etc.

11:05 And then what about therapies. Right, right. So if you're not on therapies that cause hypo, you're not going to have hypo. So the only things that are listed here sulfonylureas and insulin and as insulin is added, as more insulin is added, you get more events of hypoglycemia. Again, very common sense. So what's the story in Canada. Those were US data, let's look a Canadian data and these are data that that have been generated by Alexandra Ratzki-Leewing as well as Stewart Harris and looking at Canadian data in a very unique way. But the way that they did. It was actually through polling or surveying, I should say. And it was anonymous. So the value of something like that is it's not being reported to your physician. It's not being reported to a clinic. And I think it actually reveals some of the biases, people may have had to not disclose their hypoglycemia. At the same time, you could argue that there would be some bias for people who've chosen to participate in a survey. So I think the truth lies somewhere between these data and data that we get for randomized control trials that suggests there's not a big problem. But when you look at these data. You see, it is a big problem. So this is the risk of severe hypoglycemia, that's SH, one or more event. And this is the one year incidence. Of all people who responded 552 people those living with type one and those living with type two in the blue bars. And you can see this percentage is much higher than any of us would have expected and on the survey was clearly defined what severe hypoglycemia meant. So therefore, we would expect the respondents were taking that into account. And then if you look on the right hand side in the red, you've got the annualized severe hypoglycemia rates events per person year and the numbers here are about 2.4, 2.5. So that is high, because if you think about what I just showed you in the US it was nine events per thousand person years. And this is two and a half events per person year. So this is exponentially higher than what was seen in that US study or remember that US study was looking at hospital visits. So therefore, I think this is also telling us about things that may be happening outside of hospital. And only 34% of the respondents actually told us that they had severe hypoglycemia, us being healthcare providers. So that means what 66% do not tell us, and of those who do not tell us they are more likely to get repeated severe hypo, which again makes sense. So I think part of our job is to ask and to ask in a non judgmental way to try to promote sharing of that information.

13:56 And about 50% of the episodes of severe hypo in patients do require medical assistance. Now that medical assistance can be in the form of an EMS call, ie an a 911 call, that never goes to the hospital. And there were 189 calls to EMS per 10,000 diabetes patients per year. So it's not a tiny number right and each EMS call obviously affects our paramedics and his service and cost money. And there was a 7.4% increase in the rate of EMS calls for diabetes related emergencies from 2008 to 2014. So these are Canadian data telling us this is something we need to pay attention to. So what do we do, I think there's three things we need to do, let me start with the first thing. The first thing we need to do is identify those who are at risk. Now some of those risk factors I have shown you based on those US data. But these are the risk factors that are listed in the Diabetes Canada chapter on hypoglycemia. The first set of risk factors are things related to that person's diabetes. So if they've previously had severe hypo obviously there are higher risk of severe hypo. If they have that low A1C, although now maybe we ought to be modifying that to also say very high A1Cs are also associated. And if you've been on insulin a longer period of time, your risk is higher.

15:18 Then there are the risk factors associated with complications from diabetes. So if you've developed hypoglycemia unawareness, obviously, the chances of getting too severe or greater. Autonomic neuropathy because you’re not sensing it the same way, chronic kidney disease because of the medications that one use, the clearance of those medications as well as the disease itself. And cognitive impairment because of one's ability to recognize the hypoglycemia, and therefore adequately treat it. Then there are the social determinants of health, which are critical. So low economic status, food insecurities and low health literacy. And then there are the demographic things. So a preschool age child who is unable to recognize or unable to treat themselves. The adolescence, because of adolescence, I don't think that it's much explanation. Pregnancy because of the much lower blood sugar targets that we tend to aim for. The, the far more therapies that we tend to offer these ladies and as well pregnancy itself early on with nausea and vomiting that can contribute. And then the elderly patients often because a lot of the things above, but also age itself can impair one's ability to detect hypoglycemia. So we need to be mindful of this list and identify the patients in our practice where we need to be thinking about hypoglycemia. So we need to identify those are at risk. And then we need to minimize that risk. So how do we minimize that risk. So I think the first thing we need to do is we need to choose our therapies wisely. We should choose our therapies wisely all the time, but particularly in thinking about hypoglycemia, we need to choose them wisely. So overall, our Diabetes Canada guidelines do talk about preferentially using therapies that do not result in hypoglycemia when one of your goals is to reduce hypoglycemia. So I think that makes sense. But we know that sulfonylureas and insulin have a necessary place in our management of diabetes. And that's because in order to help achieve glycemic control in many of our patients, we will still need to use these therapies. So when using these therapies I think there are strategies we can use to try to lessen that risk. So within the sulfonylurea class, as you well know, medications like glyberide should be much lower on the list because there was are associated with higher risk of hypoglycemia compared to something like glyclizide or glucmecazide. But also our choices of insulin will make a difference. So here it's that same graph that I already showed you, but shown in a different way. Looking at the glucose lowering medications and the risk of hypoglycemia. And you can see that the reference is other medications, meaning the drugs that do not cause hypo. But sulfonylurea on its own seems to be on the lower side. Once we introduced basal insulin, it's a little bit higher. Without or with hypoglycemia, with sulfonlyruea didn't make that big of a difference. Once we introduce bolus insulin into the mix things start to go up. And then once you've got basal and bolus then things go up as well. Now, what's not shown here is pre mixed and the pre-mix story it very much depends on the individual. And as you well know, with pre mixed insulins you lack fear lack flexibility. So if someone skips a meal, their chances of hypo are much greater. So choosing our therapies wisely is very important.

18:44 And that's why within our guidelines within specific chapters, we do say that in adults with type two that are on basal insulin to lower the risk of hypoglycemia, The long acting insulin analogs, such as glargine U-100, glargine U-300, detemir, degludec, should be considered over NPH. And specifically, we say insulin degludec can be considered over insulin glargine U-100, and insulin glargine U- 300 can be considered over U-100. So in other words, recognizing that each generation of basal analog has done a good job of being flatter longer and therefore less hypo. And that includes our next generation basal analogs,  glargine U-300 and insulin decladec. And then there's the other piece about, okay, so I'm on basal insulin. I need further control do I go GLP-1 or do I go bolus insulin? And this has been established for some time now that GLP-1 basal insulin is a better option than basal insulin bolus insulin because of less hypoglycemia, and also data that shows better glycemic control. Now we know bolus insulin is still going to be needed eventually, however, as the next step after basal GLP-1 is a much smarter choice.

20:10 And therefore, one of the guidelines within our document is to say that those who are not at risk on basal… sorry not at target on basal insulin should have the addition of the GLP-1 or DPP-4 or an SGLT2 before considering the addition of prandial insulin. Now I just expect most people will already be on a DPP-4 or SGLT2 by the time basal insulin is added. And frankly, most of our practices now we'll add a GLP-1 before adding basal insulin. But for the many patients in our practice that historically are already on basal insulin than the addition of a GLP-1 is a better choice than prandial insulin. But over time, prandial insulin will still be required. So when you do need prandial or bolus insulin, what do our guidelines say. So when bolus insulin is added, rapid acting analogs, which would be your Lispro and … Oh, I'm having… Lispro, Aspart, and faster acting Aspart and glulycine, would be the ones to add because of less risk of hypoglycemia relative to regular insulin. And the other thing is when adding bolus insulin, you could also just add one shot and then over time, introduce the second and the third. So you don't have to necessarily jump right to all three meals being covered by bolus insulin. Those comments about hypoglycemia and choice of insulin apply and type two and type one diabetes, but things that are more specific to type one diabetes within our guidelines chapter is something about the real time CGM or continuous glucose monitoring. So when people with type one diabetes who are not at target, real time continuous glucose monitoring may be offered to get better control, but also to reduce the duration of hypoglycemia. But again, only if you're going to use it on a regular basis. There's also a recommendation about flash glucose monitoring, how it can also be offered to people with diabetes to decrease the time spent in hypoglycemia. And in adults with type one diabetes, having nocturnal hypoglycemia, and using insulin pump and CGM, then sensor augmented pump with low glucose suspend may be chosen again to reduce hypoglycemia. Now remember our guidelines were published in 2018 and since there have been some other important advances in the technology space, including the hybrid closed loop system. And here there are some data, looking at hybrid closed loop insulin delivery in adolescents and adults with type one diabetes. And the run-in period was the time when they were not on the hybrid closed loop. The study period is when they were on the hybrid closed loop. And you can see that the percent of time spent with blood levels less than 3.9 or less than even 2.8 for adults is significantly less using a hybrid closed loop system. So I think from a minimizing risk perspective, we need to think about the drugs we choose to use, the insulins we choose to use, the things to add to insulin and then the technologies we have to monitor glucose, but not only monitor, but actually warn and then the technologies we have to actually adjust therapy, such as hybrid closed loop.

23:36 So we need to identify the people, we need to then do something to minimize the risk, and then we need to educate and prepare because despite all of our efforts to minimize, if we're using sulfonylurea and insulin, there is still a risk of hypoglycemia. So we need to prepare our patients and prepare them well. So this brings me to the education we have to give them about how to address hypoglycemia to avoid it getting to a severe level when paramedics and emergency rooms may need to be involved. So the five steps are to recognize, to confirm, to treat, to retest, and to eat. So recognizing what hypo feels, like checking with the blood sugar to make sure it's actually under four, fast sugar (15 grams), recheck in about 15 minutes, and then eat something, what I like to call slow sugar so that it keeps the control or keeps the hypoglycemia away for a longer period of time. Now this can be done for people who are awake and alert. But what about severe hypoglycemia? Now in a conscious person, they can still treat themselves, right. So they need to treat with fast sugar, but they're going to need more, they're going to need about 20 grams. And again, they're going to retest. And again, they're going to eat. But in an unconscious person who does not have IV access, which is the vast, vast majority of the unconscious severe hypos you're going to ever encounter, then that's where glucagon comes in. As a management, one milligram of glucagon, calling 911 and discussing with the diabetes team thereafter. Now the one milligram of glucagon that's on the slide was based on 2018 when we really only had one form of glucagon to give. I think now moving forward, we would have to modify this to simply say treat with glucagon. And depending on the formulation, you're using it could be sub qim or nasal. So thinking about glucagon, then this is traditional injectable glucagon, it's to be used in an unconscious patient. The kit has to be stored in a specific way. And there are of course expiry dates that have to be considered like with all therapies. And for any of you who've tried to use glucagon, there's a preparation. Right, so it comes with a bottle with either a tablet or powder in it. There's a syringe that's already included with liquid, you have to reconstitute, mix it around, pull it up and inject. Now, for those of you on the call who are in healthcare, that's something that you've done before, even though you don't do it all the time. You've at least touched a bottle and needle a syringe. And you've probably stabbed people before. So for us, I think it's something that we would be able to do. For the average person, though, you can imagine, this would be a little bit more challenging and quite frankly terrifying. For people who have never touched a needle before and never handled those kinds of supplies. So thankfully now in Canada, we do have the nasal spray glucagon, which is an excellent advance and certainly my experience so far as my patients, it's, it's the easies, easiest conversation I ever have to have, there's really pretty much no convincing that I have to do. And I will have patients come in asking specifically for it. It's a dry powder that's just pushed up the nose. It is not an inhaler. So you don't have to time it with inhalation or anything like that. And it just absorbs through the nasal mucosa. And it's a single dose, just like with the injectable glucagon, it was a single dose. This is a single dose and it's the same dose for kids and for adults. You can leave it at room temperature. And it's to be used in children over the age of four in terms of what's been… what's in the indication in Canada. But this, you can imagine it's a whole lot easier to use for people out there.

27:18 And studies have been done on it that have shown its efficacy, which I'm not going to bother showing you, but I think this is important on a very practical level. One of the advantages in my mind and the reason why I think nasal glucagon is a no brainer is because it's a lot easier to use and the people who are going to use it, are people who never touched a needle before. The person living with diabetes is comfortable with needles, but they're not the one using it, they're passed out. It's the people around them and the average person around has never touched a needle, has never dealt with bottles has certainly never stabbed anyone, hopefully, so therefore it's hard to use. But a nasal spray, it's very easy. And here you can see even the non instructed acquaintances were able to figure it out in 26 seconds. And those who were instructed figured it out in 16 seconds versus two and a half minutes or two minutes, assuming people got it at all with the IM.

28:11 And then the other thing we have to talk about for hypoglycemia is driving. And this is advice I gave every patient of mine on an SU or on insulin and it's a conversation that that can be quick. And it's about please test before you drive. If you have any hypo, you must stop driving and then you have to treat. And technically, you need to wait 40 minutes before driving again. And the reason is because response time is impaired for 40 minutes. Have dextrose tabs in the vehicle, but not locked up in the trunk. Like it needs to be somewhere within their space that they could actually access readily. If they're going on longer trips, they should have some source of carbohydrate, other than dextrose tabs. And then, of course, those who are on real time CGM with an alarm system, lot more safety involved there. And then, if not that then FGM or flash glucose monitoring where they can actually flash and also get their reading as well. Now there's lots of resources that you can share with your patients, there's health care provider resources which are from our guidelines and then there are patient resources that are very good as well, including one specifically on driving safely. So I'd encourage you to visit the Diabetes Canada website to access those resources.

29:28 So we need to identify, we need to minimize, we need to educate, and we need to prepare. And I think if we do those things, the likelihood of one of our patients requiring hospitalization or emergency room visit or even a EMS call is going to be less. So thinking about the whole keep people out of hospital thing, we've covered now with Dr. Yu and with… Susie. And now, myself, avoiding DKA or hyperosmolar nonketotic, avoiding hyperglycemia, sick day management and now avoiding hypoglycemia. So that in a nutshell is how we're going to keep it people out of hospital.

30:14 So I'm going to switch gears now and talk a little bit about an update on COVID and diabetes and the only reason I want to do that was because the last time we spoke about this was March 20 something. It's now May 15 and things have been coming out very rapidly over the course of these two months. And I'm just going to show you some of the highlights of extra things we've learned about COVID and diabetes specifically. So the first question was the difference between susceptibility and complications when infected. And I think something that we established even at that time was that the susceptibility to get COVID-19 in someone living with diabetes seems to be similar to the general population, but complications upon infection are higher in those living with diabetes. This is taken from a epidemiologic summary that's actually available to everybody on canada.ca and gets updated on a regular basis. And this was something that I just pulled down today looking at the clinical presentations for some of the cases of COVID. You'll see that the overall number here is only 8750, which is obviously, way, way less than the actual number of cases we have in Canada. But this is these are the data publicly available as of now, and diabetes in the overall population is about 10% which is similar to that of the general population of Canada. And when we look at the breakdown by age, it also sort of fits with the numbers we see in the general population of Canada. 5% amongst those under the age of 60, I presume that's a typo, and that should be greater than or equal to 60 and about 20% in that population. So therefore, even the Canadian data would support that those living with diabetes are at the same risk of getting COVID as everyone else.

32:01 But we do know, and these were early data from China, that the case fatality rate for someone who had diabetes was higher than someone who had nothing. But this was true of all comorbidities - cardiovascular disease, chronic respiratory diseases, etc, etc. But these data are some of the earliest data, we had from the CDC in China, and since then there have been some other published reports and I'm just going to highlight a few here for you. So these are data from New York City and they're looking at 393 consecutively admitted patients in New York City. And this is just a description of the characteristics. There's no adjustment for anything. It's just, these are the numbers. And you'll see that one of the risk factors that emerged in the New York data. And as we got more data from Italy, and from the US is obesity. So obesity has now come out pretty loud and clear as a significant risk factor for more severe COVID infection and perhaps more important than diabetes, frankly. And here, when you look at obesity, you'll see that amongst those who required mechanical ventilation 43% compared to those who did not require mechanical ventilation. Hypertension has also come out as an important risk factor and other things that have come out now are age, of course, sex, meaning males seem to have more severe disease, obesity, hypertension, and as well, diabetes is still on that list. But that obesity information is interesting, those data over from the US. There were some data from Italy, but actually yesterday published on last night published online at diabetes care, there were a series of papers from China that looked at diabetes and COVID and these are 383 patients admitted to a hospital in Schengen. And they looked at BMI, now remember, this is an Asian country where obesity is not as prevalent, but yet they see a clear correlation that of those with a BMI over 28, so notice the number here is 28 in this Asian population, the multi variable model, which is shown on the far right, 3.4 is the odds ratio of progressing to severe disease compared to someone who was 18.5 to 24, which would be quote unquote normal body weight. And this was true in the overall population. True as well in men. And women, it looks like it doesn't apply, but I would not interpret it that way. The numbers of women included were less and that may explain why that correlation is not as clear.

34:38 Now why would obesity be correlated with more severe COVID infection. This is actually an excellent review article by Nitish Sattar and friends, published in circulation in April and essentially what it says is there, it's multifactorial like everything else in this world, there seems to be a direct lung thing. So people with obesity have reduced FEV1 and reduced diaphragm contractility, which may affect their, their capacity to have something go wrong with their lungs. There's of course all of the cardio metabolic problems that are associated with obesity, including diabetes and those things lead to lower cardio respiratory and metabolic reserve. On top of that excess adipose tissue may also do something bad to the immune system such that the immune response maybe hyperactive. And as you may know, one of the problems with COVID-19 infection is actually the body's attempt to fight it can then create a significant, a over response, which then results in multi organ damage, etc. So there may be something about the excess adipose tissue, which seems to spread that. And then there was a comment made about how those with obesity may actually increase viral shedding through their, their breath. I wasn't able to find a good reference for that, but that's another interesting hypothesis, all of which leads to increase severity from COVID-19 infection. So the reason I emphasize this is to say that the big question, you often get type one versus type two, does it matter? We do not yet have those data. On Twitter, I keep reading that it's coming imminently but if obesity and hypertension are significant component of the morbidity associated with COVID-19, we know that those two things are far more associated with type two diabetes than with type one diabetes. So that may help with some of the thinking around that.

36:34 On top of that, there may be a direct COVID-19 effect on the pancreas. So this is looking at ACE2 staining. Now remember ACE2 is the receptors through which COVID-19 enters the cell. And here is a stain of pancreas and just to help you, that the red parts are exocrine cells and the lighter parts are the islet cells. And when they did a control staining, you know the two parts of the pancreatic cells were not really differentiated. But once they actually immuno stained for ACE2 specifically, you'll see that it's concentrated in islet tissues and not exocrine tissues, which then poses the question does COVID-19 directly affect islet cells in the pancreas, which may then directly result in an insulin deficiency.

37:22 And then the age old question of glycemic control. Does glycemic control outside of COVID protect you when you get COVID and does glycemic control inside of COVID when you have COVID also protect you. That's really the question that I get asked a lot by patients. The short answer is we do not know for sure. There are no randomized control prospective trials to answer that question. All we can do is look at association and remember association does not prove causality but it is better than nothing. So what can I show you. So these are data from US hospitals where they collected information from patients that were using a particular glucose monitoring and insulin dosing type of system where they could then collect these kinds of data. And they looked at two categories of patients, all of whom had diabetes. One category was diabetes by A1C criteria. These are the patients who came into hospital and you knew they had diabetes. And you'll see on the left here, they came in with a mean A1C of 9.1% and then on the right hand side, there's a group of people who were found to have hyperglycemia in hospital, but we're not necessarily known to have diabetes prior and you'll see that they came in with a mean a one see of 5.9% suggesting that these people either maybe only had pre diabetes or even not even had diabetes, but they had hyperglycemia in hospital. nd what's interesting is the group who actually did not have known diabetes coming in who had marked hyperglycemia in hospital actually seem to do worse in terms of more numbers dying. Now take these data with a huge grain of salt. The numbers are very small. It's not as robust kind of data as we may hope in terms of fact checking about, you know, do they have diabetes, did they not. But it's interesting. And this suggests to me that controlling sugars in hospital is also important. Although this could just mean that those with very high sugars were sicker and therefore did worse. It's hard to tell but this is for the information we have.

39:30 And then again, fairly recently, on May 7 we got a publication from the UK looking at millions of patients that were represented in a primary care electronic health record and correlating it with those who were then  admitted to hospital with COVID. And then looking at those who passed away from COVID in hospital. And when they looked at the fully adjusted, which is probably the one we want to look at on the right, those who came in, so prior to admission for the 15 months prior to admission, those who had an A1C of 7.5% or greater had a 2.36, the hazard ratio of death was 2.36, compared to those who did not have diabetes at all. So that suggests, maybe, that having A1Cs that are lower outside seems to mean that you'll be better off, even if you did get COVID, because if you look at those who did anyone see less than 7.5 they're fully adjusted hazard ratio was only 1.5. Not proof, but an interesting observation.

40:36 And I do want to highlight this paper, which was published April 23, practical recommendations for diabetes in the age of COVID. And things around outpatient care, inpatient care, and therapeutic aims and bottom line, it's stuff that we know. It's a lot of stuff that we talked about in this webinar series through Diabetes Canada. Controlling blood sugar's yes but also teaching people about sick day management, being careful with those people, in patient. It's the stuff that you would expect treating the glycemia, avoiding steroid medications, that kind of thing, and monitoring for new onset diabetes and then therapeutic aims are similar to what they have always been. Just last night at 6pm I got the email from diabetes care of the online ahead of prints and I know it's very small print, but all of these articles are COVID related. So if you have access to diabetes care I’d encourage you to go. There was an interesting article looking at remote glucose monitoring of hospitalized quarantine patients where they actually set up areas within the hospital ward that would have, either through Carelink or through, I think that one in particular use Carelink, where they actually used the continuous glucose sensors in hospitalized patients and then you can see everybody's blood sugar's on the screen. So it's an interesting article of five places that did that. So be worth looking at.

42:03 And where can you go to get more information and where can your patients go to get more information. Of course, the Diabetes Canada website is continuously updated. But on top of that, there are now classes for our patients. There's a webinar series for people living with diabetes. There's an employer letter that's up there now that people can show their employer if they wish to have some accommodations for their diabetes and a whole bunch of really good stuff that's on there now. And for those of you who do pediatrics, this website was shown to me the other day and it's actually created by the group at McMaster Children's Hospital looking at COVID-19 and childhood, because a lot of what I've said really applies to adults or kids are a different story. And this is also kept up to date quite well, looking at COVID, type one and type two diabetes, in children.

42:53 So finally, why are we doing this? Why do we need to continue chronic disease visits? Hopefully, the answer is obvious, but this is where we are right now, right, there's going to be different waves of problems as a result of COVID. The first wave is that rush that we had about fear about ICU fear about ventilation, etc. There's a first wave which were sort of hopefully towards the end of that first wave and there may be a second wave when restrictions are being lifted as of Tuesday, but we'll see. But there's also a second wave of the influx of urgent non covert conditions, all of those elective surgeries that were planned that were postponed may no longer be elective now because of the postponement that we've had to give them. So there's this wave. And then there's this wave, which will come later. And this is our wave. This is the chronic disease exacerbation, it’s the neglecting of chronic diseases that can then results in a number of issues. And then there's a fourth wave, which is also going to be very long standing which  revolves around the mental health issues surrounding COVID pandemic itself and provider burnout, etc, etc. So these are all the various waves of problems that may in fact show up. And this one is ours and diabetes falls right into that. So it's very much our jobs to keep doing our job to help our patients and to avoid that third wave.

44:17 So to summarize, and I've left lots of time for questions. Our job, one of our jobs, is to keep people out of hospital always has been, always will be, but particularly now and Susie and Catherine went through very nicely the other components of keeping people out of hospital but on top of that, I'm going to add hypoglycemia. So remember, we want to identify, we want to minimize, we want to educate and prepare. And then specific to COVID-19 and diabetes, no increased risk of getting it, increased risk of more complicated. Glycemic control does appear to be important in COVID-19 but it's important regularly anyways. In hospital glycemic controls associated with better outcomes and pre hospital glycemic control is associated with better outcomes. So that's really where we're at in terms of our knowledge for COVID-19 and diabetes. So thank you very much for your attention. And at this point, I'm going to stop sharing and I'm going to address any questions that people may have again as a reminder, please feel free to type stuff into the chat box if any questions come up.

45:28 Is nasal glucagon available at pharmacies across Canada? The answer is yes. Nasal glucagon, I think got approval in Canada end of September of last year, if I'm not mistaken.It is in fact available across pharmacies and it is not covered on provincial formulary as of yet but are covered with the vast majority of private drug plans. What are some of the contra indications for nasal glucagon use. There is not, you’d probably have to double check the product monograph for that. Off the top of my head, I can't think of too many unless someone's nasal mucosa was not working for some reason that may be one reason, where that may not be effective. And for, that's the main thing that's coming to mind, but others may know of other contraindications, but I would certainly double check the product monograph for that. And then, I guess, children under four is not included in the indications.

46:30 Any other questions that people may have. And actually if anybody does have an answer to the contraindications question and they could type it in, that would be great. I'd have to double check the product monograph to remind myself. Well, if there are no other questions either. I was extremely clear or… Oh no. Here you go. When do we expect the third and fourth wave. So that's, that's a wonderful question, and I don't think anybody knows that for sure, but that third wave that would take longer. Right. Well, I can only speak for diabetes. Right. So in the case of diabetes, tt would be months, months down the road if there were a whole bunch of people who, let's say were not diagnosed with diabetes because they did not go to see their family doctor. They did not get blood work done. Then we may see more people showing up to emerge with DKA with newly diagnosed stuff because of the fact that they had not been diagnosed during the time they normally would have. But I think that would be months down the road. And the thing I didn't emphasize, and I should have is foot care. I'm not a foot care expert, but I know that I need to look at feet. I know that I tell my patients to please look at their feet. And right now I'm telling my patients to please look at their feet, but I'm not looking at feet because I'm not seeing people. So I think we need to remind our patients the hospitals are open, the emergency rooms are open, there is foot care that's still being provided. Please go ahead and seek treatment when you need it. Do not delay and what I'm hoping we won't see as things open up is a whole bunch of more foot wound showing up then there should have been. But again, that would be months down the road. So I think we're talking months and the fourth wave is frankly is out years because we're talking about the mental health struggles and the impact that this may have. Baqsimi is available without prescription. That's a great point. So they're available in pharmacies. They are available without prescription, because it is considered, I don't remember what the term is but essentially life saving therapy. So it is available without prescription and it's about $130 ish and then the compared to IM glucagon, which is around $90… $90 something ish.

48:57 If no need for other labs, is it worth sending patient to lab, if they're using flash meter or CGM and we can get good info from that that that is a great question. So the answer is no. The estimated A1C from both the FGM, flash glucose monitoring and the continuous glucose monitoring are quite good. But with an important caveat. It depends on the percentage of data captured. So if someone is doing flash glucose monitoring but they're only flashing twice a day, and they've got big gaps in their glucose levels that estimated A1C is not reliable. So one of the exercises I've been doing during this time is for those who are using the flash glucose monitor meter, I'm walking through it with them on the phone. If they can, I try to connect with Libreview, but not everybody has the know how or can connect to a computer. So I just walked through it with them. And one of the first things I look at is sensor usage. Because of the percent data captured is 40% well that estimated A1C is not a value to me. But every single patient where that's happened, they go, oh, I didn't realize that was only capturing 40%. And then I give them a goal. And I just made up a number, but I said I want that number to be at least 80%, 90% I mean 100% is even better. But, but I want you to check it every two weeks and work on getting that number up, up, up, up. And I think that just makes sense continuous glucose monitoring is obviously, the data don't require anybody to flash, but they need to be wearing the sensor and if they don't wear the sensor on a regular basis then again, they're not going to capture enough data. So yes, the estimated a one sees a great value and it's useful and it's reliable assuming the person is wearing the sensors long enough.

50:40 How long does nasal glucagon take to raise blood glucose compared to oral glucagon and IM glucagon. So I'm assuming you meant oral glucose and the IM glucagon. So when that head to head comparison was done, nasal glucagon was a wee bit slower, but I think the wee bit slower was in the order of a few minutes. So it's not hours later, it's a few minutes slower, but then the vast majority of people did in fact achieve a safe level of glucose to the point where they would have regained consciousness and been able to drink juice within the 15 minutes. So therefore, the difference, there is a small difference, but certainly not enough of a difference for any of the regulatory bodies to have rejected the application. So it's good enough and it takes minutes for it to start working and even though we're talking about resuming, we’re not talking about resuming to a normal glucose level we're talking to resuming to a point where they are awake and alert enough to do additional treatment. I think that's really what I'm interested in as a clinician, and as the bystander for treating some severe hypo, it's can I get this person awake and able to eat something.

52:10 Okay, so we're at 12:54 I'm going to stick around, of course, and be able to still answer your questions, but Grace, I don't know if you want to go ahead and show some of the closing slides that you had in mind.

52:23 Grace Leeder: Yes, so thank you Alice for that presentation. And if we get more questions, we'll, we'll be here until one, but I think this has been a really great series. This series really became came into fruition because of Alice’s urging and work, we think it was important to do some updates about COVID-19 and diabetes. And Alice is the chair of our professional section and these webinars have been free for anybody, any health care professional can join. They weren't limited to our membership, but if you have found them to be valuable, we would encourage you to become a professional member. Become part of our community. We have lots of groups on TimedRight that you'll be able to join in and discuss and if you have more questions or ideas or you want to look at some resources and share things, TimedRight is a really great community to do that, you'll get the Canadian Journal of Diabetes mailed to you can view all the archived versions. Hopefully when COVID kind of… when things get back to normal, we do lots of chapter events and in person events, you get a discount to the professional conference. Really good value, $105 for the year. So, the link is there diabetes.ca/health-care-providers/professional-membership to join.

Alice Cheng: Definitely join. That's my plug. Grace, there’s a couple of questions. Let me just to take those before you talk about what's coming up next.

Grace Leeder: Yeah, sure. Go ahead.

53:52 Alice Cheng: So are you recommending vitamin D supplementation and omega three fatty acid? If you're talking about vitamin D and omega three for prevention of COVID, the answer is no. None of… nothing has really, supplement wise, has been proven to help prevent COVID-19 infection or to improve its outcomes. Not hydroxychloroquine, we know, definitely not disinfectants in the body and not the UV light in the body and none of these supplements have really been shown to be effective. Do I recommend vitamin D supplementation overall, the answer is yes. For anybody living in Canada, we can all safely assume are vitamin D deficient, especially in the winter months. So yes, I do. But not for COVID. And as for omega I do not routinely recommend it either. I think the data for it are not that strong for even cardiovascular benefit. So I tend not to recommend omega. However, there's now have sort of a purified form of the EPA, which has different kind of data associated with it. If a patient does not have flash glucose monitoring what do you advise for labs in COVID times. So I do encourage people to still go to the labs, certainly in Ontario where I am the labs remain open. But by appointment only so they can go online, they can go get their blood work done there in and out. The labs are frankly more scared of the patients and the patients are the lab. So the labs are very well prepared, patients should go in with some sort of face covering and of course washing their hands. So I am still encouraging bloodwork to be done in order for us to make decisions. If somebody who's really really scared and doesn't want to go and they want to wait another month or so, I think that's reasonable. But I do remind people, though, that when things open up, those labs will get crazy busy and they'll get crazy busy because of all these people who haven't done their labs. So in some ways, you may actually want to get it done. Now, where it is by appointment only so that it is a controlled environment, as opposed to three hours sitting in a waiting room, which I think is frankly worse. So I do tell people to still go ahead and get the blood done. Okay. Grace, back to you.

56:00 Grace Leeder: Okay. So thanks so much Alice. So we have one more a webinar or COVID series next Thursday, May 21. Esmond Wong and Dr. Daniel Burton will be talking about the role of pharmacists during COVID. So talking about, sort of what can be prescribed, how to support patient’s mental health, what type of resource that the pharmacist can be for the patient during COVID. So that's next Thursday at 12pm Eastern. And thank you again Alice, this was really great and we appreciate all the work put into today's presentation.

Alice Cheng: No problem. My pleasure. Thank you very much everyone stay safe.